Rui Hao, Yiming Shao, Sisi Lin, Yi Wu, Li Bian, Yiwen Zhang
{"title":"健康中国成年人服用替比培南 Pivoxil 的生物等效性研究","authors":"Rui Hao, Yiming Shao, Sisi Lin, Yi Wu, Li Bian, Yiwen Zhang","doi":"10.1007/s40268-024-00454-w","DOIUrl":null,"url":null,"abstract":"<p><strong>Background and objective: </strong>Tebipenem pivoxil (TP) is a carbapenem and is applied against pneumonia, otitis media, and sinusitis. This study compared the pharmacokinetics (PK) and safety of a test (T) preparation and reference (R) preparation of TP in healthy Chinese adults.</p><p><strong>Methods: </strong>This study was a single-center, randomized, open, single-dose (fasting/postprandial) oral administration, two-agent, two-sequence, two-cycle, crossover bioequivalence trial. A total of 60 participants were enrolled (24 fasting and 36 postprandial). All participants were randomly assigned to the TR sequence and RT sequence. Subsequently, they switched T sequences or R sequences 7 days later. PK blood samples were collected according to the protocol, plasma TP concentration was determined by liquid chromatography-mass spectrometry, main PK parameters were calculated based on a non-compartment model, and adverse events were recorded during the test.</p><p><strong>Results: </strong>In the feeding arm, the geometric mean ratio of maximum concentration (C<sub>max</sub>) was 89.84% (90% confidence interval 84.33-95.70), the geometric mean ratio of area under the plasma concentration-time curve from time 0 to last time of quantifiable concentration (AUC<sub>0-t</sub>) was 86.80% (83.62-90.10), and the geometric mean ratio of area under the plasma concentration-time curve from time 0 to infinity time of quantifiable concentration (AUC<sub>0-∞</sub>) was 86.90% (83.73-90.20), which were within the acceptable range of bioequivalence (80-125%). In the fasting arm, the geometric mean ratio of C<sub>max</sub> was 96.07% (89.62-102.99), the geometric mean ratio of AUC<sub>0-t</sub> was 93.09% (90.47-95.78), and the geometric mean ratio of AUC<sub>0-∞</sub> was 93.09% (90.48-95.77), which was within the acceptable range of bioequivalence (80-125%). Hence, the T preparation and R preparation of TP had bioequivalence in the fasting arm and feeding arm of the clinical trial. In addition, all adverse events were mild, and no severe adverse events were noted.</p><p><strong>Conclusion: </strong>Preparations T and R of TP were bioequivalent in the fasting and postprandial groups in clinical trials, and TP was safe.</p>","PeriodicalId":49258,"journal":{"name":"Drugs in Research & Development","volume":null,"pages":null},"PeriodicalIF":2.2000,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11035523/pdf/","citationCount":"0","resultStr":"{\"title\":\"Bioequivalence Study of Tebipenem Pivoxil in Healthy Chinese Adults.\",\"authors\":\"Rui Hao, Yiming Shao, Sisi Lin, Yi Wu, Li Bian, Yiwen Zhang\",\"doi\":\"10.1007/s40268-024-00454-w\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background and objective: </strong>Tebipenem pivoxil (TP) is a carbapenem and is applied against pneumonia, otitis media, and sinusitis. This study compared the pharmacokinetics (PK) and safety of a test (T) preparation and reference (R) preparation of TP in healthy Chinese adults.</p><p><strong>Methods: </strong>This study was a single-center, randomized, open, single-dose (fasting/postprandial) oral administration, two-agent, two-sequence, two-cycle, crossover bioequivalence trial. A total of 60 participants were enrolled (24 fasting and 36 postprandial). All participants were randomly assigned to the TR sequence and RT sequence. Subsequently, they switched T sequences or R sequences 7 days later. PK blood samples were collected according to the protocol, plasma TP concentration was determined by liquid chromatography-mass spectrometry, main PK parameters were calculated based on a non-compartment model, and adverse events were recorded during the test.</p><p><strong>Results: </strong>In the feeding arm, the geometric mean ratio of maximum concentration (C<sub>max</sub>) was 89.84% (90% confidence interval 84.33-95.70), the geometric mean ratio of area under the plasma concentration-time curve from time 0 to last time of quantifiable concentration (AUC<sub>0-t</sub>) was 86.80% (83.62-90.10), and the geometric mean ratio of area under the plasma concentration-time curve from time 0 to infinity time of quantifiable concentration (AUC<sub>0-∞</sub>) was 86.90% (83.73-90.20), which were within the acceptable range of bioequivalence (80-125%). In the fasting arm, the geometric mean ratio of C<sub>max</sub> was 96.07% (89.62-102.99), the geometric mean ratio of AUC<sub>0-t</sub> was 93.09% (90.47-95.78), and the geometric mean ratio of AUC<sub>0-∞</sub> was 93.09% (90.48-95.77), which was within the acceptable range of bioequivalence (80-125%). Hence, the T preparation and R preparation of TP had bioequivalence in the fasting arm and feeding arm of the clinical trial. In addition, all adverse events were mild, and no severe adverse events were noted.</p><p><strong>Conclusion: </strong>Preparations T and R of TP were bioequivalent in the fasting and postprandial groups in clinical trials, and TP was safe.</p>\",\"PeriodicalId\":49258,\"journal\":{\"name\":\"Drugs in Research & Development\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":2.2000,\"publicationDate\":\"2024-03-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11035523/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Drugs in Research & Development\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1007/s40268-024-00454-w\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/3/7 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q3\",\"JCRName\":\"PHARMACOLOGY & PHARMACY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Drugs in Research & Development","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s40268-024-00454-w","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/3/7 0:00:00","PubModel":"Epub","JCR":"Q3","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
引用次数: 0
摘要
背景和目的：特比培南匹伏酯（TP）是一种碳青霉烯类药物，适用于治疗肺炎、中耳炎和鼻窦炎。本研究比较了中国健康成年人服用替比培南试验制剂（T）和参考制剂（R）的药代动力学（PK）和安全性：本研究是一项单中心、随机、开放、单剂量（空腹/餐后）口服、双制剂、双序列、双周期、交叉生物等效性试验。共有 60 人参加了该试验（空腹 24 人，餐后 36 人）。所有参与者都被随机分配到 TR 序列和 RT 序列。随后，他们在 7 天后更换 T 序列或 R 序列。按照方案收集 PK 血液样本，用液相色谱-质谱法测定血浆 TP 浓度，根据非室模型计算主要 PK 参数，并记录试验期间的不良事件：在喂养组中，最大浓度（Cmax）的几何平均比值为89.84%（90%置信区间为84.33-95.70），血浆浓度-时间曲线下面积从时间0到最后一次可定量浓度（AUC0-t）的几何平均比值为86.80%（83.62-90.10），血浆浓度-时间曲线下的面积（AUC0-∞）的几何平均比值为86.90%（83.73-90.20），均在生物等效性的可接受范围内（80%-125%）。在空腹组，Cmax 的几何平均比为 96.07%（89.62-102.99），AUC0-t 的几何平均比为 93.09%（90.47-95.78），AUC0-∞ 的几何平均比为 93.09%（90.48-95.77），均在生物等效性的可接受范围内（80-125%）。因此，在临床试验中，TP 的 T 制剂和 R 制剂在空腹组和进食组具有生物等效性。此外，所有不良反应均较轻微，未发现严重不良反应：结论：在临床试验中，TP 的 T 制剂和 R 制剂在空腹组和餐后组中具有生物等效性，并且 TP 是安全的。
Bioequivalence Study of Tebipenem Pivoxil in Healthy Chinese Adults.
Background and objective: Tebipenem pivoxil (TP) is a carbapenem and is applied against pneumonia, otitis media, and sinusitis. This study compared the pharmacokinetics (PK) and safety of a test (T) preparation and reference (R) preparation of TP in healthy Chinese adults.
Methods: This study was a single-center, randomized, open, single-dose (fasting/postprandial) oral administration, two-agent, two-sequence, two-cycle, crossover bioequivalence trial. A total of 60 participants were enrolled (24 fasting and 36 postprandial). All participants were randomly assigned to the TR sequence and RT sequence. Subsequently, they switched T sequences or R sequences 7 days later. PK blood samples were collected according to the protocol, plasma TP concentration was determined by liquid chromatography-mass spectrometry, main PK parameters were calculated based on a non-compartment model, and adverse events were recorded during the test.
Results: In the feeding arm, the geometric mean ratio of maximum concentration (Cmax) was 89.84% (90% confidence interval 84.33-95.70), the geometric mean ratio of area under the plasma concentration-time curve from time 0 to last time of quantifiable concentration (AUC0-t) was 86.80% (83.62-90.10), and the geometric mean ratio of area under the plasma concentration-time curve from time 0 to infinity time of quantifiable concentration (AUC0-∞) was 86.90% (83.73-90.20), which were within the acceptable range of bioequivalence (80-125%). In the fasting arm, the geometric mean ratio of Cmax was 96.07% (89.62-102.99), the geometric mean ratio of AUC0-t was 93.09% (90.47-95.78), and the geometric mean ratio of AUC0-∞ was 93.09% (90.48-95.77), which was within the acceptable range of bioequivalence (80-125%). Hence, the T preparation and R preparation of TP had bioequivalence in the fasting arm and feeding arm of the clinical trial. In addition, all adverse events were mild, and no severe adverse events were noted.
Conclusion: Preparations T and R of TP were bioequivalent in the fasting and postprandial groups in clinical trials, and TP was safe.
期刊介绍：
Drugs in R&D is an international, peer reviewed, open access, online only journal, and provides timely information from all phases of drug research and development that will inform clinical practice. Healthcare decision makers are thus provided with knowledge about the developing place of a drug in therapy.
The Journal includes:
Clinical research on new and established drugs;
Preclinical research of direct relevance to clinical drug development;
Short communications and case study reports that meet the above criteria will also be considered;
Reviews may also be considered.
京公网安备 11010802042870号
京ICP备2023020795号-1
分享
求助内容：
应助结果提醒方式：
扫码关注我们
